How do I adjust the dose of propylthiouracil (PTU) for a patient with hyperthyroidism?

Propylthiouracil (PTU) Dose Adjustment for Hyperthyroidism

The initial dose of propylthiouracil for adults with hyperthyroidism is 300 mg daily, divided into 3 equal doses taken approximately every 8 hours, with subsequent dose adjustments based on thyroid function test results to maintain free T4 or Free T4 Index in the high-normal range using the lowest possible dose. 1, 2

Initial Dosing

• For adults with standard hyperthyroidism: 300 mg daily (100 mg three times daily at 8-hour intervals) 1
• For adults with severe hyperthyroidism or very large goiters: Initial dose may be increased to 400 mg daily; occasionally patients may require 600-900 mg daily initially 1
• Monitor free T4 or Free T4 Index (FTI) every 2-4 weeks during the initial treatment phase 2

Maintenance Dosing

• The usual maintenance dose is 100-150 mg daily once clinical improvement is observed 1
• Adjust dose based on thyroid function tests to maintain free T4 or FTI in the high-normal range 2
• An elevated serum TSH indicates that a lower maintenance dose should be employed 1

Special Populations

Pediatric Patients

• Generally not recommended for pediatric patients except in rare instances when other therapies are not appropriate 1
• For children ≥6 years: Consider starting at 50 mg daily with careful upward titration based on clinical response and evaluation of TSH and free T4 levels 1
• Note that severe liver injury has been reported even with doses as low as 50 mg/day, though most cases were associated with doses of 300 mg/day and higher 1

Geriatric Patients

• Use caution when selecting doses for elderly patients 1
• Consider decreased hepatic, renal, or cardiac function, concomitant diseases, and other drug therapies 1
• May need to start with lower doses and titrate more gradually 1

Pregnant Women

• PTU is preferred over methimazole during the first trimester of pregnancy due to lower risk of birth defects 2
• Consider switching to methimazole for the second and third trimesters due to potential maternal hepatotoxicity with PTU 1
• Thyroid dysfunction often diminishes as pregnancy progresses, allowing for dose reduction or possibly discontinuation several weeks before delivery 1

Monitoring and Adjustments

• Monitor thyroid function tests periodically during therapy 1
• Obtain liver function tests if symptoms of hepatic dysfunction develop (anorexia, pruritus, jaundice, light-colored stools, dark urine, right upper quadrant pain) 1
• Consider monitoring prothrombin time during therapy, especially before surgical procedures, due to potential hypoprothrombinemia 1
• If ALT elevations occur, they are often transient and asymptomatic, allowing continued therapy with caution and close monitoring 3, 4

Managing Side Effects

• For hepatotoxicity: If mild and asymptomatic, consider continuing therapy with reduced dose and close monitoring; discontinue if symptoms develop or bilirubin increases 3, 5
• For agranulocytosis: Immediately discontinue PTU if sore throat, fever, or other signs of infection develop and obtain complete blood count 1
• For vasculitis: Discontinue PTU if symptoms such as new rash, hematuria, decreased urine output, dyspnea, or hemoptysis develop 1, 6

Adjunctive Therapy

• Beta-blockers (e.g., propranolol) can be used to control symptoms until PTU reduces thyroid hormone levels 2
• Adjust beta-blocker dose when patient becomes euthyroid, as hyperthyroidism increases clearance of these medications 1

Comparative Efficacy

• For severe hyperthyroidism (FT4 ≥7 ng/dl), methimazole 30 mg/day has been shown to normalize FT4 more effectively than PTU 300 mg/day 7
• PTU is associated with higher rates of mild hepatotoxicity compared to methimazole 7